Microbiological monitoring: European legislation

General compliance legislation:

The GMP (Eudra-Lex, Chapter 4) are the basic compliance rules for pharmaceutical companies.

Amongst these, the microbiological monitoring process is considered critical to different processes which regard sterile products. This is why GMP Annex 1 is entirely and exclusively dedicated to this kind of environments.

Annex 1, in force since 2008, is of mandatory compliance and it has set the general and basic guidelines regarding microbiological quality control in pharmaceutical facilities for the last ten years.

Likewise, it also has set as binding other international regulatory organisms standards, such as the EN or the ISO. These organisms have their own set of regulations regarding the standards which can be applicable in clean rooms.


The historical evolution of pharmaceutical companies’ needs and their technological environment have left the current Annex 1 obsolete. Therefore, a working committee, led by the MHRA, has developed a new version of Annex 1 which is currently under discussion. The published draft of the new Annex 1 includes major changes regarding its standing version.


Main comparative aspects between Annex 1 (2008) and the draft of the new Annex 1 (2018).

We would like to highlight some of the most relevant aspects that have been modified regarding the microbiological monitoring in pharmaceutical facilities:

  • One of the main points presented by the new Annex 1 draft is the fact that companies now may have a document describing the Contamination Control Strategy (CCS) throughout the organization’s environment that shows the effectiveness of the strategies, monitorization and control actions which have been applied.


  • It also presents the need to improve the environmental monitoring system (viable and non-viable particles) including scientifically-based rationales and the implementation of modern methods that optimize the detection of microbiological contamination.


  • The new Annex 1 also points to an increase of the prevention tasks, trends analysis, corrective and preventive actions (CAPA), root cause studies and any tool that can be implemented (including quick microbiology methods) to keep a steady improvement of the facilities based on the available information systems.


  • Controlling non-viable particles bigger than 5.0 µm is not going to be necessary during the qualification stages. Nonetheless, it is still necessary for routine monitorization during the use of cleanrooms as an air quality monitoring system.


  • Monitoring of air quality in grades A and B must be done continuously and during risk processes execution. This could imply the need of increasing the number of control samples according to the QRM studies performed.


  • Regulatory limits for grade A environments in the different kinds of microbiological controls have also been exposed to changes. Limit value in class A of 1 is now suggested and results averages are no longer going to be an option, this way the relevance of unusual events occurred in grade A rooms is increased.


  • Regarding the studies of trends, not only it is going to be necessary to consider the events with values higher than alert/action but also changes in trends of the contamination values or kind of flora present in the area in order to start a process of root cause investigation.


  • Staff monitoring process is going to be stricter from now on in rutine In addition, they recommend that gowning validation process should be Likewise, there is going to be an increase of the frequency and the number of sampling points.


The differences described before are still under discussion and, therefore, before there is a final official version of the document.

But what if our market is the USA or is regulated by the FDA?

In the next publication we are going to discuss the regulatory environment in the USA market and the differences between the FDA and the European regulatory environment. What are the main differences and similarities between both?  Which one are you following ?

Meanwhile, we invite you to visit our web https://sherpapharma.com/. We welcome any comment that encourages participation and technical discussion.

If you have any kind of question, do not hesitate to contact us. (info@sherpapharma.com).

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